expanded access to t-cell depleted haplo-identical stem cells for patients receiving haplo-identical and unrelated cord blood transplants

Conditions: Hematologic Malignancies; Inborn Errors of Metabolism Disorders; Immune Deficiencies

Summary: the objective of this study is to make t-cell depleted stem cells from a family member who is a half match (haplo-identical) available on an expanded access basis to patients receiving one or two unrelated cord blood transplants who are at a higher risk of not engrafting in a safe amount of time. the purpose of the related stem cells is the give the bone marrow a "jump start" towards recovery. ultimately, the cord blood cells will grow and permanently rescue the bone marrow.

the primary purpose of the study is to provide expanded access of t-cell depleted haplo-identical stem cells for patients receiving allogeneic transplantation from a related haplo-identical donor and an unrelated, umbilical cord blood (uucb) unit(s) for the treatment of high risk malignancies and non-malignant disorders. the t-cell depleted haplo-identical stems cells are intended to facilitate early, short-term myeloid engraftment with the primary goal of minimizing early infections and other non-relapse mortality while the uucb cells engraft as the durable and permanent graft. patients with high risk or refractory malignancies, or non-malignant disorders amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors will be eligible for this protocol.

Eligibility criteria:
inclusion criteria: * have a consenting related haplo-identical (3/6, 4/6, or 5/6 if drb1 mismatch) stem cell donor. * have one or two available 4, 5, or 6/6 antigen matching unrelated ucb unit(s) that will deliver a total cell dose \>3.0 x 10e7 cells/kg. patients who do not have a single ucb unit that will deliver the minimum required cell dose, two partially hla-matched ucb units which together meet the minimum cell dose requirement, can be used for 1 transplant. these units must be hla-matched minimally at 4 of 6 hla-a and b (at intermediate resolution by molecular typing) and drb1 (at high resolution by molecular typing) loci with the patient, and hla-matched at 3 of 6 hla- a, b, drb1 loci with each other (using same resolution of hla typing as indicated above). there is no limitation on maximum cell dose. * have a high risk or refractory malignancy, or non-malignant disorder amenable to stem cell transplantation therapy. * meet eligibility requirements for allogeneic transplant per institutional standard practices. * have given written informed consent according to fda guidelines (or consent of parent/legal guardian as applicable). * be \<65 years of age at the time of study enrollment. exclusion criteria: * have a consenting 8/8 or 10/10 allele matched, consenting, related or unrelated hematopoietic stem cell transplant (hsct) donor. * have a life expectancy of less than 3 months. * have uncontrolled infections at time of cytoreduction.

Keywords: haploidentical donor t-cell depleted stem cells allogeneic transplant umbilical cord blood donor high risk malignancies metabolic disorders immune deficiency acute lymphoblastic leukemia acute myelogenous leukemia myelodysplastic syndrome all aml mds cgd scid adrenoleukodystrophy metachromaticleukodystrophy krabbe pmd hunter's hurler's severe aplastic anemia lymphoma sickle cell disease thalassemia